Encouraging a move toward precision geromedicine.

Area of Science:

• Gerontology and Systems Biology
• Biomarker Discovery and Application
• Precision Medicine

Background:

• Aging is a heterogeneous, multi-system process characterized by accumulating molecular damage and declining physiological resilience.
• Individual aging trajectories diverge early due to unequal resilience distribution, leading to varied functional decline and age-related diseases.
• Early aging deviations in mitochondrial function, proteostasis, inflammation, and metabolism are often clinically silent, detectable via gerodiagnostics.

Purpose of the Study:

• To highlight the limitations of current biomarkers in quantifying aging biology and their decline in specificity with multimorbidity.
• To advocate for precision geromedicine integrating gerodiagnostics with functional reserve, behavior, physiology, and exposome measures.
• To enable identification of individualized aging trajectories and underlying biological pathways for targeted interventions.

Main Methods:

• Review and synthesis of current understanding of aging biology, damage accumulation, and resilience erosion.
• Analysis of the limitations of existing biomarkers for aging assessment versus disease detection.
• Conceptual framework development for integrating diverse data types (gerodiagnostics, functional reserve, exposome) for personalized aging analysis.

Main Results:

• Aging is driven by a dynamic interplay between ubiquitous damage accumulation and finite, unequally distributed resilience.
• Current biomarkers often detect disease rather than aging itself, with specificity decreasing in multimorbidity.
• A systems-level approach integrating gerodiagnostics, functional measures, and exposome data is crucial for understanding individual aging.

Conclusions:

• Precision geromedicine necessitates integrating gerodiagnostics that assess system-level resilience and stress responsiveness.
• This integrated approach allows for the identification of individualized aging trajectories and causal pathways.
• Individualized gerointerventions can modify aging trajectories by targeting identified pathways, moving beyond disease-specific treatments.